Emodin Regulates Apoptotic Pathway in Human Liver Cancer Cells
Emodin Regulates Apoptotic Pathway in Human Liver Cancer Cells
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DOI：
10.1002/ptr.4703
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发表时间：
2013-02
影响因子：
7.2
通讯作者：
Jianqing Yu;Wei Bao;Jiachuan Lei
中科院分区：
文献类型：
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作者：
Jianqing Yu;Wei Bao;Jiachuan Lei
大黄素是一种天然蒽醌类化合物，在多种肿瘤细胞中具有抗增殖作用。然而，对人类肝癌的抗癌机制仍不清楚。在这项研究中，我们观察到大黄素诱导HepG 2细胞凋亡，并导致细胞在G1期的显着积累。Western blot结果显示，大黄素处理后，细胞色素c从线粒体释放到胞浆中的量增加，caspase-8和caspase-9活化，提示大黄素可能通过内源性和外源性途径参与细胞色素c的合成。大黄素处理还导致细胞内活性氧的剂量依赖性积累。大黄素还可上调HepG 2细胞p53蛋白表达，下调NF-κB/p65蛋白表达，提示这两种调节因子可能在大黄素诱导HepG 2细胞凋亡中发挥作用。计算模型表明大黄素可以通过与Bcl-2的Ala 146残基形成一个氢键直接与Bcl-2的BH 3结构域结合。从这些检查中，大黄素不仅显著下调Bcl-2的表达，而且由于大黄素和Bcl-2之间的强相互作用，还抑制Bcl-2与Bax的异二聚化。这些结果表明大黄素诱导肝癌细胞凋亡是一个多方面的复杂级联反应。版权所有© 2012约翰威利父子有限公司.
Emodin, a natural anthraquinone, has been reported to possess antiproliferative effects in many cancer cell lines. However, anticancer mechanism against human liver cancer remains unclear. In this study, we observed that emodin induced apoptosis in HepG2 cells and caused a significant accumulation of cells in the G1 phase. Western blot data showed that emodin treatment caused the increasing of release of cytochrome c into cytosol from mitochondria and the activation of caspase‐8 and caspase‐9, which suggest that the intrinsic and extrinsic pathways could be involved. Emodin treatment also resulted in a dose‐dependent accumulation of intracellular reactive oxygen species. Furthermore, emodin increased the protein level of p53 and decreased the protein level of NF‐κB/p65 in HepG2 cells, which indicated these two regulators might play a role in emodin‐induced apoptosis. Computational modeling showed that emodin could directly bind to the BH3 domain of Bcl‐2 through forming one hydrogen bond with Ala146 residue in Bcl‐2. From these examinations, emodin not only significantly downregulated expression of Bcl‐2 but also inhibited the heterodimerization of Bcl‐2 with Bax because of strong interaction between emodin and Bcl‐2. These suggest that emodin induces apoptosis in liver cancer cell line through a multifaceted complex cascade of events. Copyright © 2012 John Wiley & Sons, Ltd.